Design of Macromolecular Complexes

Research Area D

In this research area, we will challenge our insights of specific macromolecular complexes gained in CEF-I. We will deduce predictions about how to modify protein complex function, and test and realize these predictions experimentally. We made important achievements in a number of subjects that led us to define research area D as a new emerging field in CEF-II. We will achieve exogenous and precise control of macromolecular function using optogenetics and chemical biology, to organize components of macromolecular complexes in time and space such that their interactions can be controlled or triggered. We have established the use of rhodopsins to manipulate cellular membrane potential by light and to trigger cellular function, e.g. in neurons. We will combine rhodopsins with endogenous channel complexes to achieve new light-triggered currents. As membrane transport complexes require energy to perform their function, we will alter the energy transduction modes that in nature utilize the membrane potential, to light- and ATP-driven systems. Modular multienzymatic "assembly lines" will be altered to generate molecular factories for specific compounds. Approaches in Area D require know-how in protein modeling and design, various spectroscopic methods, electron microscopy, structural biology, photobiology, and atomic force microscopy.

Strategic Goals:

• Optogenetics: Controlling membrane potential and cell activity by light• Small molecules, engineered protein and nucleic acid switches to control action and organization of macromolecular complexes• (Re-)Design of macromolecular complexes→ use these tools to study macromolecular complexes in action